Enantioselective Rhodium‐Catalyzed Coupling of Arylboronic Acids, 1,3‐Enynes,and Imines by Alkenyl‐to‐Allyl 1,4‐Rhodium(I) Migration

A chiral rhodium complex catalyzes the highly enantioselective coupling of arylboronic acids, 1,3‐enynes, and imines to give homoallylic sulfamates. The key step is the generation of allylrhodium(I) species by alkenyl‐to‐allyl 1,4‐rhodium(I) migration.     

Arylative Intramolecular Allylation of Ketones with 1,3-Enynes Enabled by Catalytic Alkenyl-to-Allyl 1,4-Rhodium(I) Migration

Alkenyl-to-allyl 1,4-rhodium(I) migration enables the generation of nucleophilic allylrhodium(I) species by remote C−H activation. This new mode of reactivity was employed in the diastereoselective reaction of arylboron reagents with substrates containing a 1,3-enyne tethered to a ketone, to give products containing three contiguous stereocenters. The products can be obtained in high enantioselectivities using a chiral sulfur-alkene ligand.     

Enantioselective Rhodium‐Catalyzed Coupling of Arylboronic Acids, 1,3‐Enynes,and Imines by Alkenyl‐to‐Allyl 1,4‐Rhodium(I) Migration

A chiral rhodium complex catalyzes the highly enantioselective coupling of arylboronic acids, 1,3‐enynes, and imines to give homoallylic sulfamates. The key step is the generation of allylrhodium(I) species by alkenyl‐to‐allyl 1,4‐rhodium(I) migration.     

Regioselective Intermolecular Allylic C−H Amination of Disubstituted Olefins via Rhodium/π‐Allyl Intermediates

A method for catalytic intermolecular allylic C−H amination of trans ‐disubstituted olefins is reported. The reaction is efficient for a range of common nitrogen nucleophiles bearing one electron‐withdrawing group, and proceeds under mild reaction conditions. Good levels of regioselectivity are observed for a wide range of electronically diverse trans ‐β‐alkyl styrene substrates.     

Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group

Rhodium(I)‐catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh?C(sp²) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ‐bond metathesis of a tethered O?H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.     

Asymmetric Catalytic Formal 1,4‐Allylation of β,γ‐Unsaturated α‐Ketoesters: Allylboration/Oxy‐Cope Rearrangement

A highly enantioselective formal conjugate allyl addition of allylboronic acids to β,γ‐unsaturated α‐ketoesters has been realized by employing a chiral Ni^II/N,N′‐dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy‐Cope rearrangement sequence, providing a facile and rapid route to γ‐allyl‐α‐ketoesters with moderate to good yields (65–92 %) and excellent ee values (90–99 % ee). The isolation of 1,2‐allylboration products provided insight into the mechanism of the subsequent oxy‐Cope rearrangement reaction: substrate‐induced chiral transfer and a chiral Lewis acid accelerated process. Based on the experimental investigations and DFT calculations, a rare boatlike transition‐state model is proposed as the origin of high chirality transfer during the oxy‐Cope rearrangement.     

Palladium‐Catalyzed Directed meta‐Selective C−H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates

Palladium(II)‐catalyzed meta‐selective C?H allylation of arenes has been developed utilizing synthetically inert unactivated acyclic internal olefins as allylic surrogates. The strong σ‐donating and π‐accepting ability of pyrimidine‐based directing group facilitates the olefin insertion by overcoming inertness of the typical unactivated internal olefins. Exclusive allyl over styrenyl product selectivity as well as E stereoselectivity were achieved with broad substrate scope, wide functional‐group tolerance, and good to excellent yields. Late‐stage functionalisations of pharmaceuticals were demonstrated. Experimental and computational studies shed light on the mechanism and point to key steric control in the palladacycle, thus determining product selectivities.     

Catalytic Enantioselective Synthesis of 1,4‐Keto‐Alkenylboronate Esters and 1,4‐Dicarbonyls

A catalytic enantioselective method for the synthesis of 1,4‐keto‐alkenylboronate esters by a rhodium‐catalyzed conjugate addition pathway is disclosed. A variety of novel, bench‐stable alkenyl gem‐diboronate esters are synthesized. These easily accessible reagents react smoothly with a collection of cyclic α,β‐unsaturated ketones, generating a new C?C bond and stereocenter. Products are isolated in up to 99 % yield with greater than 20:1 E/Z and greater than 99:1 e.r. Mechanistic studies show the site‐selectivity of transmetalation and reactivity is ligand dependent. The utility of the approach is highlighted by gram‐scale synthesis of enantioenriched cyclic 1,4‐diketones, and stereoselective transformations of the products by hydrogenation, allylation, and isomerization.     

Asymmetric Alkenylation of Enones and Imines Enabled by A Highly Efficient Aryl to Vinyl 1,4‐Rhodium Migration

The asymmetric rhodium‐catalyzed alkenylation of enones and imines with arylboronic acids has been developed. A highly controllable aryl to vinyl 1,4‐rhodium migration is the key step. Stereodefined vinyl moieties were installed in excellent enantioselectivies for most examined examples. DFT calculations reveal that the driving force of this rhodium migration is a kinetically favored process.     

Microwave‐Assisted Synthesis of Heterocycles by Rhodium(III)‐Catalyzed Annulation of N‐Methoxyamides with α‐Chloroaldehydes

α‐Chloroaldehydes have been used as alkyne equivalents in rhodium‐catalyzed syntheses of isoquinolones and 3,4‐dihydroisoquinolins starting from N ‐methoxyamides. Compared to the existing technology, a complementary regioselectivity is achieved. Mechanistic investigations have been performed, and it was found that steric effects of both substrate and additive determine the product selectivity. Various other heterocycles, such as isoquinolines and lactones, can be prepared by transformation of the obtained products.     

Catalytic 1,4‐Rhodium(III) Migration Enables 1,3‐Enynes to Function as One‐Carbon Oxidative Annulation Partners in CH Functionalizations

1,3‐Enynes containing allylic hydrogens cis to the alkyne are shown to act as one‐carbon partners, rather than two‐carbon partners, in various rhodium‐catalyzed oxidative annulations. The mechanism of these unexpected transformations is proposed to occur through double C? H activation, involving a hitherto rare example of the 1,4‐migration of a Rh^III species. This phenomenon is general across a variety of substrates, and provides a diverse range of heterocyclic products.